Using DNA microarray analyses to elucidate the effects of genistein in androgen‐responsive prostate cancer cells: Identification of novel targets

Abstract

Many studies have correlated the consumption of soy-rich diets with a decreased risk of developing hormone-dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybean and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we used a DNA microarray approach to examine the effects of genistein at concentrations in the physiologic range on global gene expression patterns in androgen-responsive cancer cells. Microarray analyses were performed on androgen-responsive LNCaP human prostate cancer cells exposed to 0, 1, 5, or 25 microM genistein. We found a concentration-dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor (AR)-mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we propose that the regulation of AR-mediated pathways is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels.

Perspectives on the Role of Isoflavones in Prostate Cancer

“…Cluster analyses (35) revealed that genistein regulates the expression of genes that are critically involved in the regulation of apoptosis, cell cycle, cellular signaling, angiogenesis, invasion, and metastasis. A similar pleiotropic action of genistein on multiple signaling pathways was observed when cDNA microarray studies were conducted using LNCaP cells (36).…”

No Effect of Red Clover–Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer

“…In contrast, in vitro studies using androgen-responsive prostate cancer cells showed that genistein, daidzein, and equol all consistently inhibit IGF-IR mRNA expression, even at relatively low levels of exposure (i.e., being comparable to human dietary intake; refs. 43,44). In cultured HT-29 human colon cancer cells, genistein, but not daidzein, was found to reduce IGF-IR protein levels and inhibit IGF-IR signaling at relatively high pharmacologic concentrations (45).…”

Chronic quercetin exposure affects fatty acid catabolism in rat lung

“…For example, they are strong antioxidants [2,3], inhibit tumor formation [4], improve endothelial function [5,6] and affect energy metabolism [7]. To elucidate the molecular mechanisms explaining the beneficial effects of flavonoids observed in vivo, several studies have employed a systems biology approach with transcriptomics and proteomics techniques, using cell culture systems [8][9][10][11][12][13][14][15][16][17][18]. However, these in vitro studies may have generated misleading findings due to the non-physiological exposure conditions mostly used.…”